BACKGROUND: Long-acting somatostatin analogues have been suggested as an alternative to propranolol for the prevention of variceal rebleeding. AIM: To compare the effectiveness of lanreotide SR, a new depot formulation injected once-weekly, and propranolol in reducing circadian portal blood flow (PVF) and meal-stimulated hepatic venous pressure gradient (HVPG) in patients with liver cirrhosis. METHODS: Patients were randomized to receive either lanreotide SR intramuscularly (30 mg once weekly, n=12) or propranolol (n=12) orally. Hemodynamic measurements were performed on day 0 and on day 21 after a 3-week period of drug administration, while patients received three standard oral liquid test meals. On each study day 27 PVF measurements were performed over 24 h and eight measurements of HVPG during the first postprandial period. RESULTS: Propranolol was more effective than lanreotide SR in reducing baseline HVPG (-21.9 vs. -13.6%, P=0.04) and meal-stimulated HVPG (-16.6 vs. -3.8%, P=0.04). Propranolol reduced circadian PVF significantly by 9.3% (P=0.03) but not lanreotide SR. CONCLUSIONS: Long-term treatment with propranolol reduced baseline and postprandial HVPG and circadian PVF, while lanreotide SR did not. The results of our study do not encourage clinical testing of lanreotide SR 30 mg for the prevention of variceal haemorrhage.